Eukaryotic peptide chain release factor GTP-binding subunit ERF3A (GSPT1)

The protein contains 499 amino acids for an estimated molecular weight of 55756 Da.

 

Involved in translation termination in response to the termination codons UAA, UAG and UGA (By similarity). Stimulates the activity of ETF1 (By similarity). Involved in regulation of mammalian cell growth (PubMed:2511002). Component of the transient SURF complex which recruits UPF1 to stalled ribosomes in the context of nonsense-mediated decay (NMD) of mRNAs containing premature stop codons (PubMed:24486019). Required for SHFL-mediated translation termination which inhibits programmed ribosomal frameshifting (-1PRF) of mRNA from viruses and cellular genes (PubMed:30682371). (updated: Sept. 18, 2019)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  6. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 94%
Model score: 99

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The reference OMIM entry for this protein is 139259

G1- to s-phase transition 1; gspt1
Gst1, yeast, homolog of; gst1
Peptide chain release factor 3a; erf3a
Etf3a

CLONING

Kikuchi et al. (1988) isolated a gene from a yeast genomic library that could complement a temperature-sensitive mutant of Saccharomyces cerevisiae. The gene, termed GST1, seemed to be essential for the G1- to S-phase transition in the yeast cell cycle. The gene product appeared to be a GTP-binding protein of molecular mass 76,565 Da with 38% identity in amino acid sequence with the alpha subunit of elongation factor-1 (130590). Hoshino et al. (1989) cloned the human equivalent from a cDNA library. Hoshino et al. (1998) cloned mouse Gspt1. The deduced 635-amino acid protein has a unique N terminus and a conserved C-terminal eukaryotic elongation factor-1-alpha-like domain. The mouse and human Gspt1 proteins share 94% sequence identity. RT-PCR analysis indicated expression of Gspt1 in all mouse tissues examined.

GENE FUNCTION

Eukaryotic RF1 (ETF1; 600285) and RF3 are involved in translation termination. In vitro, RF1 catalyzes the release of the polypeptide chain without any stop codon specificity; the GTP-binding protein RF3 confers GTP dependence to the termination process and stimulates RF1 activity. Le Goff et al. (1997) used tRNA-mediated nonsense suppression of different stop codons in a CAT reporter gene to analyze the polypeptide chain release factor activities of recombinant human RF1 and RF3 proteins overexpressed in human cells. Using a CAT assay, they measured the competition between the suppressor tRNA and the release factors when a stop codon was present in the ribosomal A site. Regardless of which of the 3 stop codons was present in the CAT open reading frame, the overexpression of RF1 alone markedly decreased translational read-through by suppressor tRNA. Thus, Le Goff et al. (1997) concluded that RF1 has intrinsic antisuppressor activity. The levels of antisuppression when both RF1 and RF3 were overexpressed were almost the same as those when RF1 was overexpressed alone, suggesting that RF1-RF3 complex-mediated termination may be controlled by the expression level of RF1. Overexpression of RF3 alone had an inhibitory effect on CAT gene expression. CAT mRNA stability studies suggested that RF3 inhibits gene expression at the transcriptional level. Le Goff et al. (1997) suggested that RF3 may perform other functions, including the stimulation of RF1 activity, in vivo. Hoshino et al. (1998) found that expression of Gspt1 by Swiss 3T3 cells increased with serum or phorbol ester stimulation. By coimmunoprecipitation and yeast 2-hybrid analyses, they found interaction between mouse Gspt1 and human eRF1. Hoshino et al. (1998) hypothesized that Gspt1, in a binary complex with eRF1, functions as a polypeptide chain release factor. Alkalaeva et al. (2006) reconstituted eukaryotic translation initiation, elongation, and termination processes in vitro on a model mRNA encoding a tetrapeptide followed by a UAA stop codon using individual 40S and 60S ribosomal subunits and the complete set of individual initiation, elongation, and release factors. They found that binding of human ERF1 and ERF3A and GTP to the ribosomal pretermination complex induced a structural rearrangement characterized by a 2-nucleotide forward shift of the toeprint attributed to the pretermination complex. Subsequent GTP hydrolysis was required for rapid hydrolysis of peptidyl tRNA in the pretermination complex. Cooperativity between ERF1 and ERF3A in ensuring fast peptidyl-tRNA hydrolysis required the ERF3A-binding C-terminal domain ... More on the omim web site

Subscribe to this protein entry history

Sept. 22, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.

Jan. 21, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

June 20, 2017: Protein entry updated
Automatic update: comparative model was added.

March 25, 2017: Additional information
No protein expression data in P. Mayeux work for GSPT1

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 139259 was added.

Jan. 24, 2016: Protein entry updated
Automatic update: model status changed